RG-1530   Click here for help

GtoPdb Ligand ID: 10361

Synonyms: compound 2 [PMID: 24900658] | R-1530 | R1530 | RG1530
Compound class: Synthetic organic
Comment: RG-1530 is an orally active multikinase inhibitor, with a high affinity for polo like kinase 4 (PLK4). Its PLK4 inhibitory action was expoited for antiproliferative potential [1-4]. PLK4 is expressed at very low levels in normal cells, but its expression can be upregulated in cancer cells where it localises to the centriole and is essential for controlling centriole duplication and mitotic progression. This makes PLK4 an ideal target for disrupting mitosis in cancer cells.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 2
Hydrogen bond donors 2
Rotatable bonds 2
Topological polar surface area 66.59
Molecular weight 356.08
XLogP 5.83
No. Lipinski's rules broken 1
SMILES / InChI / InChIKey
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Canonical SMILES COc1cc2[nH]c3n[nH]c(c3nc(c2cc1F)c1ccccc1Cl)C
Isomeric SMILES COc1cc2[nH]c3n[nH]c(c3nc(c2cc1F)c1ccccc1Cl)C
InChI InChI=1S/C18H14ClFN4O/c1-9-16-18(24-23-9)21-14-8-15(25-2)13(20)7-11(14)17(22-16)10-5-3-4-6-12(10)19/h3-8H,1-2H3,(H2,21,23,24)
InChI Key UOVCGJXDGOGOCZ-UHFFFAOYSA-N
Bioactivity Comments
RG-1530 inhibits mutliple kinases in vitro, but only FLT1 and FLT3 have binding affinities (Kd values) ≤ than the Kd for PLK4 (11nM) [4]. In the KinomeScan assay 31 of the 178 tested kinases gave a Kd <500 nM.
Selectivity at enzymes
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Target Sp. Type Action Value Parameter Concentration range (M) Reference
polo like kinase 4 Hs Inhibitor Inhibition 8.0 pKd - 4
pKd 8.0 (Kd 1.1x10-8 M) [4]
Janus kinase 2 Hs Inhibitor Inhibition 7.5 pKd - 4
pKd 7.5 (Kd 2.9x10-8 M) [4]
aurora kinase A Hs Inhibitor Inhibition 7.0 pKd - 4
pKd 7.0 (Kd 9.6x10-8 M) [4]
Selectivity at catalytic receptors
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Target Sp. Type Action Value Parameter Concentration range (M) Reference
fms related receptor tyrosine kinase 1 Hs Inhibitor Inhibition 8.1 pKd - 4
pKd 8.1 (Kd 9x10-9 M) [4]
fms related receptor tyrosine kinase 3 Hs Inhibitor Inhibition 8.0 pKd - 4
pKd 8.0 (Kd 1.1x10-8 M) [4]
kinase insert domain receptor Hs Inhibitor Inhibition 7.8 pKd - 4
pKd 7.8 (Kd 1.5x10-8 M) [4]
ret proto-oncogene Hs Inhibitor Inhibition 7.7 pKd - 4
pKd 7.7 (Kd 2.2x10-8 M) [4]
KIT proto-oncogene, receptor tyrosine kinase Hs Inhibitor Inhibition 7.6 pKd - 4
pKd 7.6 (Kd 2.6x10-8 M) [4]